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RNA helicase DDX1 converts RNA G-quadruplex structures into R-loops to promote IgH class switch recombination

MPG-Autoren
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Meinhart,  Anton
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

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Zitation

de Almeida, C. R., Dhir, S., Dhir, A., Moghaddam, A. E., Sattentau, Q., Meinhart, A., et al. (2018). RNA helicase DDX1 converts RNA G-quadruplex structures into R-loops to promote IgH class switch recombination. Molecular Cell, 1-22. doi:10.1016/j.molcel.2018.04.001.


Zitierlink: http://hdl.handle.net/21.11116/0000-0001-4A7A-4
Zusammenfassung
Class switch recombination (CSR) at the immunoglobulin heavy-chain (IgH) locus is associated with the formation of R-loop structures over switch (S) regions. While these often occur co-transcriptionally between nascent RNA and template DNA, we now show that they also form as part of a post-transcriptional mechanism targeting AID to IgH S-regions. This depends on the RNA helicase DDX1 that is also required for CSR in vivo. DDX1 binds to G-quadruplex (G4) structures present in intronic switch transcripts and converts them into S-region R-loops. This in turn targets the cytidine deaminase enzyme AID to S-regions so promoting CSR. Notably R-loop levels over S-regions are diminished by chemical stabilization of G4 RNA or by the expression of a DDX1 ATPase-deficient mutant that acts as a dominant-negative protein to reduce CSR efficiency. In effect, we provide evidence for how S-region transcripts interconvert between G4 and R-loop structures to promote CSR in the IgH locus.